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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.1
- 수록면
- 151 - 156 (6page)
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RAD51 recombinase plays a critical role in homologous recombination and DNA damage repair. Here we showed that expression of RAD51 is frequently upregulated in lung cancer tumors compared with normal tissues and is associated with poor survival (hazard ratio (HR) = 2, P = 0.0009). Systematic investigation of lung cancer cell lines revealed higher expression of RAD51 in KRAS mutant (MT) cells compared to wildtype (WT) cells. We further showed that MT KRAS, but not WT KRAS, played a critical role in RAD51 overexpression via MYC. Moreover, our results revealed that KRAS MT cells are highly dependent on RAD51 for survival and depletion of RAD51 resulted in enhanced DNA double strand breaks, defective colony formation and cell death. Together, our results suggest that mutant KRAS promotes RAD51 expression to enhance DNA damage repair and lung cancer cell survival, suggesting that RAD51 may be an effective therapeutic target to overcome chemo/radioresistance in KRAS mutant cancers.
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참고문헌 (28)
참고문헌 신청
Blandin Knight S / 2017 / Progress and prospects of early detection in lung cancer / Open Biol 7:170070
Kaufman J / 2017 / Treatment of KRAS-Mutant Non-Small Cell Lung Cancer : The End of the Beginning for Targeted Therapies / JAMA 317:1835~1837
Matikas A / 2017 / Targeting KRAS mutated non-small cell lung cancer : A history of failures and a future of hope for a diverse entity / Crit Rev Oncol Hematol 110:1~12
Cox AD / 2015 / Targeting RAS membrane association: back to the future for anti-RAS drug discovery? / Clin Cancer Res 21:1819~1827
De Roock W / 2011 / KRAS, BRAF, PIK3CA, and PTEN mutations : implications for targeted therapies in metastatic colorectal cancer / Lancet Oncol 12:594~603
Kaufman J / 2017 / Treatment of KRAS-Mutant Non-Small Cell Lung Cancer : The End of the Beginning for Targeted Therapies / JAMA 317:1835~1837
Matikas A / 2017 / Targeting KRAS mutated non-small cell lung cancer : A history of failures and a future of hope for a diverse entity / Crit Rev Oncol Hematol 110:1~12
Cox AD / 2015 / Targeting RAS membrane association: back to the future for anti-RAS drug discovery? / Clin Cancer Res 21:1819~1827
De Roock W / 2011 / KRAS, BRAF, PIK3CA, and PTEN mutations : implications for targeted therapies in metastatic colorectal cancer / Lancet Oncol 12:594~603
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Extracellular signal-regulated kinase 5 increases radioresistance of lung cancer cells by enhancing the DNA damage response
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Effects of Tumor Microenvironmental Factors on DNA Methylation and Radiation Sensitivity in A549 Human Lung Adenocarcinoma
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돌연변이 p53 단백질의 Silencing에 의한 사람유방암세포의 in vivo 항종양 효과
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DNA damage response revisited: the p53 family and its regulators provide endless cancer therapy opportunities
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DNA end resection and its role in DNA replication and DSB repair choice in mammalian cells
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Novel discrimination system for lung cancer cell with virus based color structure
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